Adhesive Laminates for Rapid Wound Occlusion

ABSTRACT

Provided herein are protective laminate devices comprising a biocompatible non-adherent substance and a fast-setting adhesive and methods of use. Also provided is a dispenser for an adhesive tape. The protective laminate devices and methods may be used for wound closure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This divisional application claims benefit of priority under 35 U.S.C.§120 of pending divisional application U.S. Ser. No. 13/291,619, filedNov. 8, 2011, which claims benefit of priority under 35 U.S.C. §120 ofcontinuation application U.S. Ser. No. 12/804,292, filed Jul. 19, 2010,now U.S. Pat. No. 8,053,052, which claims benefit of priority under 35U.S.C. §120 of non-provisional application U.S. Ser. No. 11/032,427,filed Jan. 10, 2005, now U.S. Pat. No. 7,758,939, which claims benefitof priority under 35 U.S.C. §119(e) of provisional application U.S. Ser.No. 60/534,917, filed Jan. 8, 2004, now abandoned, then entirety of allof which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the fields of biomedicalengineering, biochemistry and surgical procedures. More specifically,the present invention provides a device and methods using woundlaminates and occlusive coatings suitable for sealing tissues orenhancing wound healing.

2. Description of the Related Art

Conventional methods of wound closure following surgery consist ofapplying sutures or staples to join two or more tissues that have beendissected. Various alternative methods have been developed to fastentissues together without the use of a conventional staple or suture.Commercial electrosurgery and electrocautery devices, which employ heat,are often used for sealing external and internal wounds. Other ways forsealing vessels using other forms of electromagnetic energy, such asthat produced by lasers, are known.

Tissue adhesives consisting of biomolecules, such as fibrin, currentlyare used to “glue” tissue-to-tissue. The results are often sub-optimaldue to weak adherence and dissolution of the fibrin clot. Cyanoacrylatesof various types, derived from instant bonding glues, e.g., SUPERGLUE™,also are used on tissue and available for use in the home, althoughcurrently they are approved only in the United States for external use.DERMABOND™, an approved topical skin adhesive, is 2-octyl cyanoacrylatewith added colorant D&C Violet #2 for easy visualization. The packageinsert for this material warns that any inadvertent contact with anybody tissue and any surfaces or equipment, such as latex gloves orstainless steel, should be avoided. The adhesive is applied by apposingthe tissue edges with fingers or forceps and applying the liquidadhesive in several stroking motions not unlike that used with apaintbrush, allowing time to dry in between strokes.

Practically, there is a significant problem with the use of fast-settingskin adhesives. Bonding may result in unintentional bonding of human orinanimate applicators. During application of cyanoacrylate-basedadhesives the care provider often glues his or her examination gloves tothe patients. Unintentional bonding requires the bonded materials to bepeeled apart potentially causing local trauma. Acetone is a solvent ofcyanoacrylate that can help loosen the bond, but the use of acetone onan open wound can be problematic. Furthermore, DERMABOND™ is notindicated for use in high-tension skin areas, where it's holding forcemay be insufficient to maintain wound closure, or near the eyes whererunoff of the glue may result in unintentional adhesion.

The inventors have recognized a need in the art for an improvement inthe devices and methods used for joining tissues separated throughsurgery or through trauma. The prior art is deficient in the lack offast-setting adhesives and the use thereof in minimizing the risk ofunintentional bonding during use of these fast-setting adhesives. Thepresent invention fulfills this longstanding need and desire in the art.

SUMMARY OF THE INVENTION

The present invention is directed to a laminate device for protecting anadhesive during manipulation thereof. The laminate device comprises anadhesive and at least one layer of a biocompatible non-adherentsubstance disposed in protective relationship to the adhesive. Thepresent invention is directed to a device further comprising at leastone removable layer disposed in contact with the adhesive, with one ormore layers of the biocompatible non-adherent substance or a combinationthereof. The present invention also is directed further to a devicecomprising an emulsifying agent, a solubilizing agent, a wetting agent,a taste modifying agent, a plasticizer, a bioactive agent, a watersoluble inert filler, a preservative, a buffering agent, a coloringagent, a stabilizer, or a combination thereof and/or a pharmaceutical inone or more biocompatible non-adherent layers.

The present invention also is directed to a method of preventingunintentional bonding of an adhesive during application thereof to oneor more tissues. The laminate device described herein is positioned onthe tissue(s) such that the adhesive layer comprising the laminatedevice is in contact with the tissue(s) and activating the adhesive. Theremoval of the removable layer(s) comprising the laminate device isdependent upon the disposition of the removable layer within thelaminate device. If the removable layer is disposed only on a surface ofthe adhesive layer, the removable layer is removed prior to positioningthe laminate device. If the removable layer(s) is disposed on one ormore layers of the biocompatible non-adherent substance comprising thelaminate device, the removable layer(s) is removed after activating theadhesive or a combination thereof. The biocompatible non-adherentsubstance and the removable layer(s) protect the adhesive layer duringapplication thereof thereby preventing unintentional bonding of theadhesive. The method further may comprise setting the adhesive to jointhe tissues.

The present invention is directed further to a method of delivering abioactive agent to one or more tissues. The laminate device describedherein is positioned upon the tissue(s) where one or more of the layersof the laminate device comprises the bioactive agent thereby deliveringthe bioactive agent to the tissue(s). The present invention is directedfurther to a related method where the bioactive agent is the adhesivecomprising the layer in contact with the tissue(s) whereby setting theadhesive joins the tissue(s). The present invention is directed furtherto another related method where the bioactive agent is a pharmaceuticalcomprising one or more of the layers of the laminate device describedherein disposed in protective relationship with a porous or permeableadhesive layer in contact with the tissue(s) whereby the pharmaceuticaldiffuses therefrom through the porous or permeable adhesive layer.

The present invention is directed further still to a dispenser for anadhesive tape. The dispenser comprises a biocompatible non-adherentsubstance, a means to dispense an adhesive layer onto a layer of thebiocompatible non-adherent substance, a means to cut the combinedlayers, and a housing having an opening.

The present invention is directed further still to a method of formingan adhesive tape to join one or more tissues. A length of the layer ofthe biocompatible non-adherent substance is withdrawn through theopening in the dispensor described immediately supra whilesimultaneously dispensing the adhesive layer along the length of thelayer of the biocompatible non-adherent substance via the brush in thedispensor. The combined layers are cut via the cutting means comprisingthe dispenser after sufficient length has been withdrawn thereby formingthe adhesive tape. Additionally, the method provides for positioning theadhesive tape on one or more tissues such that the adhesive layer is incontact with the tissue(s) and setting the adhesive thereby joining thetissue(s).

Other and further aspects, features, and advantages of the presentinvention will be apparent from the following description of thepresently preferred embodiments of the invention given for the purposeof disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the matter in which the above-recited features, advantages andobjects of the invention, as well as others that will become clear, areattained and can be understood in detail, more particular descriptionsof the invention briefly summarized above may be had by reference tocertain embodiments thereof that are illustrated in the appendeddrawings. These drawings form a part of the specification. It is to benoted, however, that the appended drawings illustrate preferredembodiments of the invention and therefore are not to be consideredlimiting in their scope.

FIGS. 1A-1C depict an adherent tissue patch without a non-stickremovable layer (FIG. 1A) and with a non-stick removable layer (FIGS.1B-1C).

FIG. 2 depicts an adherent tissue patch positioned over a laceration onthe dorsal aspect of a hand.

FIGS. 3A-3B depict an adhesive patch comprising a reservoir containing abioactive material incorporated within the patch and a porous adhesivelayer (FIG. 3A) or a permeable adhesive layer (FIG. 3B).

FIG. 4 depicts an adherent tissue patch dispenser.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment of the present there is provided a laminate device forprotecting an adhesive during manipulation thereof, comprising theadhesive; and at least one layer of a biocompatible non-adherentsubstance disposed in protective relationship to the adhesive. In thisembodiment the laminate device may comprise a patch.

Further to this embodiment the laminate device may comprise at least oneremovable layer disposed in contact with the adhesive, with one or morelayers of the biocompatible non-adherent substance or a combinationthereof. In one aspect of this embodiment the removable layer isdisposed in contact with the adhesive and is removable prior tomanipulation of the adhesive. In another aspect the removable layer isdisposed between the adhesive and the biocompatible non-adherentsubstance and is removable after manipulation of the adhesive. In yetanother aspect the removable layer is disposed in a coveringrelationship to an outer layer of the biocompatible non-adherentsubstance and is removable after manipulation of the adhesive. Theremovable layer may comprise teflon or a cellulose impregnated with alipid. Examples of the lipid are lecithin, polyethylene glycol or a wax.

In all aspects of this embodiment the biocompatible non-adherentsubstance dissolves upon contact with a fluid, e.g., water. Thebiocompatible non-adherent substance may be a hydrocolloid such aspullulan. Additionally, in all aspects of this embodiment the adhesivemay comprise a cyanoacrylate or a derivative thereof, a protein or asynthetic polymer. Furthermore the adhesive may be porous or permeable.

In one aspect of this embodiment the biocompatible non-adherentsubstance may be disposed on a surface of the adhesive. In anotheraspect one or more layer(s) of the biocompatible non-adherent substancemay comprise the adhesive incorporated therein. In a related aspect theadhesive may be contained within a rupturable reservoir within one ofthe layer(s).

In related aspects one or more layers of the biocompatible non-adherentsubstance further may comprise an emulsifying agent, a solubilizingagent, a wetting agent, a taste modifying agent, a plasticizer, anactive agent, a water soluble inert filler, a preservative, a bufferingagent, a coloring agent, an aesthetic design, a stabilizer, or acombination thereof. In another related aspect one or more layers of thebiocompatible non-adherent substance further comprises a pharmaceutical.In yet another related aspect the pharmacutical may be contained withina rupturable reservoir within the layer(s).

In another embodiment of the present invention, there is provided amethod of preventing unintentional bonding of an adhesive duringapplication thereof to one or more tissues, comprising positioning thelaminate device described herein onto the tissue(s) where the adhesivelayer comprising the laminate device is in contact with the tissue(s);activating the adhesive; and removing the removable layer(s) comprisingthe laminate device, where, if the removable layer is disposed only on asurface of the adhesive layer, then removable layer is removed prior topositioning said laminate device or if the removable layer(s) isdisposed on one or more layers of the biocompatible non-adherentsubstance comprising the laminate device, then the removable layer(s) isremoved after activating the adhesive or a combination thereof; whereinthe biocompatible non-adherent substance and the removable layer(s)protect the adhesive layer during application thereof thereby preventingunintentional bonding of the adhesive.

Further to this embodiment the method comprises setting the adhesive tojoin the tissue(s). In this embodiment the layers of the biocompatiblenon-adherent substance and the additional agents added thereto, theadhesive layer, the removable layers and the disposition of the layerswithin the laminate device are as described supra. Additionally, thebiocompatible non-adherent substances and the adhesives are as describedsupra.

In yet another embodiment of the present invention, there is provided amethod of delivering a bioactive agent to one or more tissues,comprising positioning the laminate device described herein in contactwith said tissue(s) wherein one or more of the layers of the laminatedevice comprises said bioactive agent thereby delivering said bioactiveagent to the tissue(s).

In an aspect of this embodiment the bioactive agent is an adhesivecomprising the layer in contact with the tissue(s). The method furthercomprises setting the adhesive to join the tissues. In a related aspectthe adhesive may be contained within a rupturable reservoir. The methodfurther comprises rupturing the reservoir prior to setting the adhesive.

In another aspect of this embodiment the bioactive agent is apharmaceutical comprising one or more of the layers disposed inprotective relationship with a porous or permeable adhesive in contactwith the tissue(s). The method further comprises diffusing thepharmaceutical from the layer(s) through the porous or permeableadhesive layer. In a related aspect the pharmaceutical may be containedwithin a rupturable reservoir. The method further comprises rupturingthe reservoir prior to diffusing the adhesive. In all aspects of thisembodiment the laminate device and the adhesive are as described supra.

In still another embodiment of the present invention, there is provideda dispenser for an adhesive tape, comprising a biocompatiblenon-adherent substance; a means to dispense an adhesive layer onto alayer of the biocompatible non-adherent substance; a means to cut thecombined layers; and a housing having an opening. The biocompatiblenon-adherent substance, the layer thereof and the additional agentsadded thereto and the adhesive are as described supra.

In one aspect of this embodiment the means to dispense the adhesivecomprises a brush impregnated with the adhesive. In a related aspect themeans to dispense the adhesive comprises a brush and an ampoule tocontain the adhesive fluidly connected to the brush.

In still another embodiment of the present invention, there is provideda method of forming an adhesive tape to join one or more tissues,comprising withdrawing a length of the layer of the biocompatiblenon-adherent substance through the opening in the dispensor describedsupra; simultaneously dispensing the adhesive layer along the length ofthe layer of the biocompatible non-adherent substance via the brush inthe dispensor and cutting the combined layers via the cutting meanscomprising the dispenser after sufficient length has been withdrawnthereby forming the adhesive tape. Further to this embodiment the methodprovides for positioning the adhesive tape on one or more tissues suchthat the adhesive layer is in contact with the tissue(s) and setting theadhesive thereby joining the tissue(s).

Provided herein are protective adherent devices, patches or adhesivetapes to join and aid the joining of biological tissues by adhesion. Thepatch or tape includes a fast-setting adhesive or other type of tissueadhesive and a shield or laminate(s) that are at least in part comprisedof a protective layer(s) that preferentially dissolve upon exposure tobody fluids or water. Additional layers of the patch may includepharmaceuticals or other biologics. Also provided is a device todispense the tape comprising a biocompatible laminate and fast-settingadhesive. The protective patches or tapes and dispensors may be used forclosing a wound following trauma or a surgical procedure.

A tissue patch may comprise a protective layer of a laminate or shieldcomprising a non-adherent biocompatible material placed in contact witha fast-setting adhesive layer. The adhesive is, preferably, acyanoacrylate, or is derived from the cyanoacrylates, but also mayinclude other synthetic and naturally-occurring adhesives used intissues. Included are protein adhesives, e.g. fibrin, collagen, andactivated adhesives, such as those used in laser tissue welding.

Optionally, the non-adherent biocompatible material may dissolve inwater. The biocompatible material may be a hydrocolloid material and maycomprise a carbohydrate, such as pullulan. The biocompatible materialcomprising the shield or laminate may be, inter alia,poly(DL-lactic-co-glycolic acid), whey-protein emulsion with sorbitol,glycerol with butterfat and candelilla wax, arabinoxylans andhydrogenated palm kernel oil, calcium caseinate and whey protein,carboxymethylcellulose, pectin, milk-protein, or resins. Alternatively,the biocompatible material may be coated with a non-stick material, suchas, but not limited to, a lipid, on the surface that comes into contactwith the adhesive and so can be immediately removed from the adhesiveupon polymerization of the latter.

A non-dissolving biocompatible laminate or shield may be placed incontact with a fast-setting adhesive to form a tape. The non-dissolvingbiocompatible laminate is textured with a plurality of projections toaid in wound closure. The projections provide means to manually drawapposed tissue toward the dissection line without necessity of forceps.

Additionally, the laminate tissue patch may comprise a non-stickremovable layer to prevent inadvertent adhesion to the adhesive. Thenon-stick removable layer may be positioned in contact with thedissolvable biocompatible laminate which is in contact with thefast-setting adhesive layer to form a tissue tape. Alternatively, thelaminate tissue patch may comprise a dissolvable biocompatible materialas an upper layer which is in contact with the fast-setting adhesivelayer. The other side of the fast-setting adhesive is covered with theremovable layer which prevents inadvertent sticking to the patch. Theremovable layer may be peeled away to expose the fast-setting adhesiveprior to positioning the tissue patch on the individual.

The removable layer may comprise materials which do not stick to thefast-setting adhesive. For example, if the fast-setting adhesive iscyanoacrylate, the removable layer may comprise teflon or celluloseimpregnated with a lipid, e.g. lecithin or wax. Representative lipidsare lecithin or polyethylene glycol, and representative waxes areparaffin, beeswax, candelilla, carnauba, or ceresine.

The tissue patch may fasten at least two substrates in order to effect abond between the substrates in an individual, in a plant or animal or incells and tissues of other organisms. The patch is useful forapproximating apposed edges of dissected tissue, for compromisinginfected tissue, for holding pharmaceuticals in place, or for occludingopen wounds, iatrogenic or otherwise, for the purpose of minimizing thechance of infection. The biocompatible shield or laminate is intended toprevent the care-provider from inadvertently sticking him/herself to theadhesive material and yet will dissolve upon exposure to water withoutundesirable toxicity to the individual. Potentially corrosive, toxic, orotherwise undesirable material is shielded from contact with a human orinanimate applicator, thus allowing the applicator to manipulate thematerials with greater freedom.

Generally, the protective layer or shield, either biocompatible or not,may comprise in part or in whole a hydrocolloid. Preferably, thehydrocolloid comprises a water soluble natural polysaccharide orderivatives, including pectin and derivatives, guar gum arabic,tragacanth gum, xanthan gum, gellan sodium salt, propyleneglycolalginate, starches (amylose, amylopectin), modified starches,hydroxyethyl starch, pullulan, carboxymethyl starch, gum ghatti, okragum, karaya gum, dextrans, dextrins and maltodextrins, konjac, acemannanfrom aloe, locust bean gum, tara gum, quince seed gum, fenugreek seedgum, scleroglucan, gum arabic, psyllium seed gum, tamarind gum, oat gum,quince seed gum, carrageenans, scleraglucan, succinoglucan, larcharabinogalactan, flaxseed gum, chondroitin sulfates, hyaluronic acid,curdlan, chitosan, deacetylated konjac, and rhizobium gum.

The hydrocolloid may be a water soluble non-gelling polypeptide orprotein exemplified by gelatins, albumins, milk proteins, soy protein,and whey proteins. The hydrocolloid further may be selected from a groupof synthetic hydrocolloids exemplified by polyethyleneimine,hydroxyethyl cellulose, sodium carboxymethyl cellulose, carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose,methyl cellulose, ethyl cellulose, polyacrylic acids, low molecularweight polyacrylamides and their sodium salts (carbomers),polyvinylpyrollidone, polyethylene glycols, polyethylene oxides,polyvinyl alcohols, pluronics, tetronics, and other block co-polymers,carboxyvinyl polymers, and colloidal silicon dioxide.

Suitable hydrocolloids or mixtures producing synergistic propertiescomprise natural seaweeds, natural seed gums, natural plant exudates,natural fruit extracts, biosynthetic gums, gelatines, biosyntheticprocessed starch or cellulosic materials, alginates, agar gum, guar gum,locust bean gum (carob), carrageenan, tara gum, gum arabic, ghatti gum,Khaya grandifolia gum, tragacanth gum, karaya gum, pectin, arabian(araban), xanthan, gellan, starch, Konjac mannan, galactomannan,funoran, are xanthan, acetan, gellan, welan, rhamsan, furcelleran,succinoglycan, scleroglycan, schizophyllan, tamarind gum, curdlan,pullulan, and dextran

Additionally, the biocompatible laminate or shield may comprise any orall of emulsifying agents, solubilizing agents, wetting agents, tastemodifying agents, plasticizers, active agents, water soluble inertfillers, preservatives, buffering agents, coloring agents, andstabilizers. Addition of a plasticizer to the formulation can improveflexibility. The plasticizer or mixture of plasticizers may bepolyethylene glycol, glycerol, sorbitol, sucrose, corn syrup, fructose,dioctylsodiumsulfosuccinate, triethylcitrate, tributylcitrate,1,2-propylenglycol, mono-, di- or triacetates of glycerol, or naturalgums. Preferred plasticizers are glycerol, polyethylene glycol,propylene glycol, citrates and their combinations. The amount ofplasticizer depends on the final application.

Examples of natural water-soluble polymers include plant-type polymers,microorganism-type polymers and animal-type polymers. A plant-typepolymer may be gum arabic, gum tragacanth, galactan, guar gum, carobgum, karaya gum, carrageenan, pectin, agar, quince seed or Cydoniaoblonga, algae colloids such as brown algae extract, starches such asrice, corn, potato, and wheat, and glycyrrhizic acid. Microorganism-typepolymers may be xanthan gum, dextran, succinoglucan, and pullulan.Animal-type polymers may be collagen, casein, albumin, and gelatin.

Examples of the semisynthetic water-soluble polymers include starch-typepolymers, cellulosic polymers and alginic acid-type polymers.Starch-type polymers may be carboxymethyl starch and methylhydroxypropylstarch. Cellulosic polymers may be methyl cellulose, ethyl cellulose,methylhydroxypropyl cellulose, hydroxyethyl cellulose, cellulose sodiumsulfate, hydroxypropyl cellulose, carboxymetyl-cellulose, sodiumcarboxymethyl cellulose, crystal cellulose, and cellulose powder.Alginic acid-type polymers may be sodium alginate and\propyleneglycol-alginate.

Examples of the synthetic water-soluble polymers include vinyl polymers,polyoxyethylene-type polymers, acrylic polymers, and cationic polymers,and polyethyleneimine. Vinyl polymers may be polyvinyl alcohol,polyvinyl methyl ether, polyvinylpyrrolidone, carboxy vinyl polymer.Polyoxyethylene-type polymers may be a copolymer of polyethylene glycol20,000, 40,000, or 60,000 and polyoxyethylene polyoxypropylene. Acrylicpolymers may be sodium polyacrylate, polyethylacrylate, andpolyacrylamide.

Thickeners may include gum arabic, carrageenan, karaya gum, gumtragacanth, carob gum, quince seed or Cydonia oblonga, casein, dextrin,gelatin, sodium pectate, sodium alginate, methyl cellulose, ethylcellulose, CMC, hydroxy ethyl cellulose, hydroxypropyl cellulose, PVA,PVM, PVP, sodium polyacrylate, carboxy vinyl polymer, locust bean gum,guar gum, tamarind gum, cellulose dialkyl dimethylammonium sulfate,xanthan gum, aluminum magnesium silicate, bentonite, hectorite, AIMgsilicate or beagum, laponite, and silicic acid anhydride.

Additionally, the present invention provides a shield or laminate for anadhesive or an adhesive laminate whereby an external layer of the shieldmay dissolve upon contact with fluids. The soluble, external shield mayserve as an applicator to facilitate the application of the adhesive totissue. The shield or laminate also may comprise one or more internallayers, reservoirs or pooled materials containing the adhesive.Furthermore multiple layers or reservoirs may contain a biologic, a drugor other pharmaceutical substance, whereby the system becomes a drugdelivery device. The bioactive material may be, although not limited to,one of or a combination of nitroglycerin, an anti-nauseant, anantibiotic, a hormone, a steroidal anti-inflammatory agent, anon-steroid antiinflammatory agent, a chemotherapeutic agent, ananti-cancer agent, an immunogen, an analgesic, an anti-viral agent or ananti-fungal agent.

The layers used as a barrier to separate the adhesive from the backing,or the adhesive from the substrate, may be removed upon application.Alternatively, a layer may be designed to allow for release of theactive agent, e.g., adhesive or biologic, drug or other pharmaceuticalsubstance, upon activation, whereby the activation consists ofcompromising the layer. Examples include perforation, or dissolutionupon exposure to fluids or heat, e.g.

body heat, thus allowing the active agent to flow past the barrier.Alternatively, the adhesive layer may be separate from the barrier layerand may be porous or permeable whereby, upon mechanically compromisingthe integrity of a reservoir contained within the barrier layer orlaminate, a bioactive material, such as a pharmaceutical, is released todiffuse through the adhesive layer.

The present invention provides dispensers for the laminates andadhesives described herein. The dispenser may hold the laminate, aportion of which is withdrawn from the dispenser as needed. Thefast-setting adhesive is applied to a side of the laminate whereupon thedispenser is used to cut the laminate. This provides an adhesive tapeused to effect a bond between the substrates in an individual.Alternatively, a dispenser may dispense a fast-setting adhesivecontiguous with the laminate. When the adhesive dispenser ismechanically disrupted, the adhesive flows into the laminate.

As described below, the invention provides a number of therapeuticadvantages and uses, however such advantages and uses are not limited bysuch description. Embodiments of the present invention are betterillustrated with reference to the FIGS. 1-5, however, such reference isnot meant to limit the present invention in any fashion. The embodimentsand variations described in detail herein are to be interpreted by theappended claims and equivalents thereof.

FIGS. 1A-1C depict examples of adherent tissue patches. In FIG. 1A thetissue patch 12 comprises a protective layer 14, which is a non-adherentbiocompatible material and optionally water soluble, the inferiorsurface of which is disposed on and in contact with the superior surfaceof a fast-setting adhesive layer 16, such as cyanoacrylate.Alternatively, the biocompatible material 14 may be coated with anon-stick material (not shown), such as a lipid, on the inferior surfacethat comes into contact with the adhesive 16, and so can be immediatelyremoved from the adhesive 16 upon polymerization of the latter.

FIG. 1B depicts a tissue patch 12 comprising a biocompatible material14, the inferior surface of which is disposed on and in contact with thesuperior surface of a fast-setting adhesive layer 16. The superiorsurface of the biocompatible material 14 is disposed on and in contactwith the inferior surface of a covering material 18 that allows the careprovider to apply downward force to the patch 12 and not contaminate thebiocompatible material 14. The covering material 18 may be peeled awayfrom the biocompatible material 14 after application of the patch 12 tothe tissue (not shown).

Alternatively, in FIG. 1C, a patch 12 comprises a biocompatible material14, the inferior surface of which is disposed on and in contact with thesuperior surface of a fast-setting adhesive layer 16. The inferior sideof the fast-setting adhesive 16 is in contact with and covered by aremovable layer 20 intended to prevent inadvertent sticking to the patch12. Peeling away the removable layer 20 at position 22 exposes thefast-setting adhesive 14 prior to positioning the patch 12 on theindividual. The removable layer 20 may comprise materials which do notstick to the fast-setting adhesive 14.

With continued reference to FIG. 1A, FIG. 2 depicts a laminate adhesivepatch 12, which has a shape that allows application to the substrates,e.g., a hand 50 with wound 55, in a way that the apposed edges 52,54 ofthe wound 50 may be drawn together without the use of forceps or withoutinadvertent adhesion of the care-provider to the patch 12. A first part32 of the patch 12 may be applied to the side of the wound 50 havingwound edge 52. A second part 34 of the patch 12 may be applied to theside of the wound 50 having wound edge 54 to maintain close contactbetween the apposed wound edges 52,54. The patch 12 further comprises anadditional plurality of parts 36 joining the first and second parts32,34 of the patch 12 which maintain tension across the wound 50 thusminimizing dihescence. Optionally, parts 36 may shrink with theapplication of heat

Still with continued reference to FIG. 1A, FIG. 3A depicts a laminateadhesive patch 12 comprising a biocompatible material 14, which has aninternal reservoir 60 containing bioactive material 70, the inferiorsurface of which is disposed on and in contact with the superior surfaceof a porous biocompatible adhesive layer 62 comprising a fast-settingadhesive 64 and perforations 66 between the superior and inferiorsurfaces of the porous biocompatible layer 62. Upon mechanicallycompromising the integrity of the reservoir 60, the bioactive material70 diffuses through the porous layer 62 and is beneficially delivered tothe tissue (not shown) on which the patch 12 is applied.

FIG. 3B depicts a laminate adhesive patch 12 comprising a biocompatiblematerial 14, which has an internal reservoir 60 containing bioactivematerial 70, the inferior surface of which is disposed on and in contactwith the superior surface of a permeable biocompatible adhesive layer 68comprising a fast-setting adhesive 64. The adhesive layer 68 is of sucha composition that the bioactive material 70 can permeate through. Theremainder of the patch 12 dissolves upon being exposed to water. Thebioactive material 70 can be a pharmaceutical.

Again with continued reference to FIG. 1A, FIG. 4 depicts a dispenser 80comprising a roll 82 of biocompatible material 14 which can be drawn,through manual effort, from the dispenser 80. When the biocompatiblematerial 14 is drawn from the dispenser 80, it contacts brush 84, orother applicator, which is impregnated with the fast-acting adhesive 16.The adhesive 16 coats the biocompatible material 14 as it contacts brush84, thus forming an adhesive tape 90. A cutter 86 cuts adhesive tape 90when an appropriate length has been drawn through the dispenser 80.

Optionally, the dispenser 80 may comprise a receptacle 88 to contain thefast-acting adhesive 16 which may polymerize rapidly upon contact withair and/or moisture. Recepticle 88 may be broken open manually, forexample, as with a glass ampoule, prior to use of the dispensor 80. Uponbreaking the recepticle 88, the adhesive 16 flows into the brush 84. Thebrush 84 is impregnated with adhesive 16 and can apply the adhesive 16to the biocompatible material 14.

The following examples are given for the purpose of illustrating variousembodiments of the invention and are not meant to limit the presentinvention in any fashion.

EXAMPLE 1 Inhibition of Cyanoacrylate Polymerization

A drop of commercial industrial fast-drying cyanoacrylate adhesive wasaliquoted onto a small piece of Parafilm-M (Pechiney Plastic Packaging,Chicago Ill.) and onto a teflon cooking pan and left in ambient roomconditions. In each case, the cyanoacrylate failed to polymerize. Thisresult was unexpected as the cyanoacrylate is normally considered tocombine with moisture in the air and thereby polymerize when in contactwith virtually anything, as long as air is present.

EXAMPLE 2 Flexible Hot-Melt Adhesive

Several pieces of a gummi-type confectionary (Haribo Gummi-Bears) wereslowly melted in a glass beaker at approximately 60° C. A sample ofapproximately 1 ml was placed on a standard glass microscope slide andanother slide was then placed in contact with the molten material,overlapping the first slide by about 1 inch and left to dry overnight.The next day, it was impossible to manually separate the two microscopeslides, although a small amount of movement was possible due to theelastic nature of the adhesive.

EXAMPLE 3 Hot-Melt Adhesive Sticks to PTFE

Approximately 20 g of Haribo Gummi-Bears was slowly melted in a glassbeaker at approximately 60° C. A mixture of 75% ovalbumin in water wasstirred into the confectionary while it was still molten. Samples of thestill molten adhesive was placed on teflon (PTFE) cooking pans andpressed down with a teflon plate weighing 1 kg. In one case, a thin filmof mineral oil was spread over the PTFE plate prior to application ofthe adhesive. In another case, a small amount of plastisizer (5%pullulan) was added to the molten mixture prior to application on thePTFE plate.

After allowing to cure overnight, the 1 kg teflon plates were removedand an attempt was made to manually remove the adhesive from theunderneath PTFE cooking pan. In all cases, the adhesive adhered verystrongly to the plate, which is surprising as only a few materials areknown to adhere to teflon. The adhesive with plastisizer stuck best andcouldn't be removed, while the adhesive without plastisizer would onlybe removed by scraping it off with a spatula-like device.

EXAMPLE 4

Ablation of Stratum Corneum with Cyanoacrylate

A drop of commercial industrial fast-drying cyanoacrylate (Krazy Glue)was aliquoted onto a small piece of clear acetate film. The film wasthen inverted and placed on the dorsum of a volunteer's forearm. After aperiod of 2 minutes, a corner of the acetate was raised and the entirepiece was rapidly removed from the skin. It was apparent that at leastpart of the stratum corneum was removed and was left on the acetatesheet, along with any hair that was present on the skin at the treatmentsite. Application to the ablation site of 200 microliters of 1%lidocaine with epinephrine for 5 minutes and subsequent probing of thesite with a 25G hypodermic needle gave evidence of some degree ofanesthesia. The epinephrine caused a blanching of the skin, as measuredby a Minolta chromameter. These results are clear evidence of stratumcorneum ablation with the cyanoacrylate and film laminate.

EXAMPLE 5 Biocompatible Films

Several different formulations of thin films were tested for variousdesirable mechanical properties such as thickness, strength, elasticityand water-solubility: (1) 11% aqueous solution of pullulan; (2) 6%aqueous solution of pullulan with 2.5% aqueous gelatin; (3) 3% aqueoussolution of pullulan with approximately 11% glycerol and 3.8% PEG8000(polyethylene glycerol with a molecular weight of 8000) added; and (4)6% aqueous solution of pullulan with 0.3% aqueous iota-carageenen.Aliquots of the four test films were applied to a PTFE cooking plate andleft to dry overnight. All of the dried samples varied between 0.06 and0.15 mm in thickness.

Sample 1 was smooth and quite strong, while sample 2 had undesirablebubbles and was more fragile. Sample 3 was strong and much more flexiblethan sample 1, while sample 4 was also flexible, but not as smooth asthe other samples. None of the samples adhered strongly to the PTFEplate. One film with excellent properties as a laminate film was madeout of water, pullulan, PEG8000, and glycerol. Other concentrations ofthese four components were tested which provided superior flexibility,elasticity and uniformity in thickness. Other potentially useful filmswere made up of pullan (e.g. 5%) and iota-carageenen (e.g. 0.38%). Allsamples subsequently dissolved well in water, although at differingrates.

EXAMPLE 6 More Biocompatible Films

Several more formulations of thin films were tested for variousdesirable mechanical properties: (1) 10% aqueous lambdacarageenen-results after drying overnight: elastic, flexible and withhigh tensile strength; (2) 0.75% aqueous lambda carageenen with 25%glycerol-results after drying overnight: sticks well to PTFE plate, butnot to fingers; (3) 0.5% aqueous lambda carageenen with 0.5%PEG8000-results after drying overnight: very uniform, strong andflexible, but slightly retarded dissolving time in water; (4) 5% aqueouspullulan and 0.5% lambda carageenen-results after drying overnight:strong and flexible, but not very elastic, good solubility in water,adheres to moist tissue readily); (5) 10% aqueous hydroxypropylcellulose-results after drying overnight: very strong and flexible,slightly elastic, vinyl-like; (6) 0.86% aqueous lambda carageenen and14% glycerol-results after drying overnight: elastic, doesn't adhere todry tissue readily but adheres readily to moist tissue; (6) 2.5% aqueoushydroxypropyl cellulose, 5% lambda carageenen and 2.5% pullulan-resultsafter drying overnight: strong and flexible, slightly elastic, goodsolubility in water.

EXAMPLE 7 Thin Film Adhesive Shields

Several thin films were prepared for the purpose of shielding adhesives.Cyanoacrylate glues were applied to human skin or to wood strips, thencovered with thin films prepared from formulations comprised primarilyof pullulan and lambda-carageenan. Polysorbate-A was added in lowconcentrations in some formulations. Thin films were prepared by mixingpullulan (5-10% w/v), lambda-carageen (0.1-0.5% w/v) and polysorbate-A(0-0.1% v/v). In some samples food coloring was added to improvevisibility.

Samples (15 ml) were applied to the center of 7 cm diameter plasticrings and the material was allowed to dry overnight, resulting in thinfilms (approx. 20-50 micron thickness) with good flexibility andsolubility characteristics. Upon further evaluation, it was demonstratedthat the shields could be applied to the surface of cyanoacrylate glues,as well as other adhesives, and then washed from the surface followingcuring of the glue, with no apparent alteration of the glue.

EXAMPLE 8 Thin Film Adhesive Laminates

Multi-layer laminates were prepared for the purpose of shieldingadhesives and improving the adherence of the laminate to tissues. Inthis experiment, the adhesive shield was prepared as in Examples 5-7.Various films then were applied to one another prior to complete drying.In these experiments, films prepared as described in Examples 5 and 6were allowed to reach 75-95% dryness before layering with the shieldmaterial prepared as in example 7. This resulted in laminates withdifferent properties on each side.

The adhesive shield on one side allowed the material to be manipulatedfreely, while the other side provided for other properties, such astissue adherence. At times, adhesives were sandwiched between the twofilms in order to provide a complete system. With this type of laminate,an adhesive material may be applied to the surface of moist membranouswounds, such that the tissue adhering layer immediately sticks to thetissue, thereby immediately localizing the adhesive at the wound site,while a protective layer shields the applicator from the adhesive

One skilled in the art will appreciate readily that the presentinvention is well adapted to carry out the objects and obtain the endsand advantages mentioned, as well as those objects, ends and advantagesinherent herein. The present examples, along with the methods,procedures, treatments, molecules, and specific compounds describedherein are presently representative of preferred embodiments, areexemplary, and are not intended as limitations on the scope of theinvention. Changes therein and other uses will occur to those skilled inthe art which are encompassed within the spirit of the invention asdefined by the scope of the claims.

What is claimed is:
 1. A dispenser for an adhesive tape, comprising: abiocompatible non-adherent substance; a means to dispense an adhesivelayer onto a layer of said biocompatible non-adherent substance; a meansto cut said combined layers; and a housing having an opening.
 2. Thedispenser of claim 1, wherein said biocompatible non-adherent substancedissolves upon contact with a fluid.
 3. The dispenser of claim 1,wherein one or more layers of said biocompatible non-adherent substancecomprises a hydrocolloid.
 4. The dispenser of claim 1, wherein the layerof said biocompatible non-adherent substance further comprises anemulsifying agent, a solubilizing agent, a wetting agent, a tastemodifying agent, a plasticizer, a bioactive agent, a water soluble inertfiller, a preservative, a buffering agent, a coloring agent, astabilizer, or a combination thereof.
 5. The dispenser of claim 1,wherein said adhesive is cyanoacrylate or a derivative thereof, aprotein or a synthetic polymer.
 6. The dispenser of claim 1, wherein themeans to dispense said adhesive comprises a brush impregnated with saidadhesive.
 7. The dispenser of claim 1, wherein the means to dispensesaid adhesive comprises: a brush; and an ampoule to contain saidadhesive fluidly connected to said brush.
 8. A method of forming anadhesive tape to join one or more tissues, comprising: withdrawing alength of the layer of said biocompatible non-adherent substance throughthe opening in the dispensor of claim 1; simultaneously dispensing theadhesive layer along the length of the layer of said biocompatiblenon-adherent substance via the brush in said dispensor; and cutting thecombined layers via the cutting means comprising said dispenser aftersufficient length has been withdrawn thereby forming said adhesive tape.9. The method of claim 8, further comprising: positioning said adhesivetape on one or more tissues, said adhesive layer in contact with saidtissue(s); and setting said adhesive thereby joining said tissue(s).